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Showing drug card for Hyaluronidase (DB00070)

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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-02-19 16:03:24
Primary Accession Number DB00070
Secondary Accession Number
  • BIOD00022
  • BTD00022
Name Hyaluronidase
Drug Type
  • Approved
  • Biotech
  • Investigational
Description Highly purified sheep hyaluronidase for administration by injection into the vitreous of the eye.
Synonyms
  1. Hyal-1
  2. Hyaluronidase 1 precursor
  3. Hyaluronidase PH-20
  4. Sperm adhesion molecule 1
  5. Sperm surface protein PH-20
  6. hyaluronidase
Brand Names
  1. Vitragan
  2. Vitrase
  3. Vitrase (Ista Pharma)
Brand Mixtures Not Available
Chemical IUPAC Name Sheep hyaluronidase
Chemical Formula C2455H3775N617O704S21
Chemical Structure Structure
Protein Sequence(s) >DB00070 sequence
LNFRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDR
LGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWA
RNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHL
WGYYLFPDCYNHHYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAAT
LYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASG
IVIWGTLSIMRSMKSCLLLDNYMETILNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSS
DYLHLNPDNFAIQLEKGGKFTVRGKPTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAV
DVCIADGVCIDAFLKPPMETEEPQIFYNASPSTLSATMFIVSILFLIISSVASL
CAS Registry Number 488712-31-8
InChI Identifier Not Available
InChI Key Not Available
KEGG Drug Not Available
KEGG Compound Not Available
PubChem Compound Not Available
PubChem Substance Not Available
ChEBI ID Not Available
PharmGKB ID PA449893 Link Image
HET ID Not Available
GenBank ID L13781 Link Image
Drug ID Number [DIN] 02041278 Link Image
RxList Link http://www.rxlist.com/cgi/generic/hylenex.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Hyaluronidase Link Image
FDA Label
Material Safety Data Sheet (MSDS)
Synthesis Reference Not Available
Average Molecular Weight 53870.9000
Monoisotopic Molecular Weight Not Available
State Liquid
Melting Point Not Available
Experimental Water Solubility Not Available Source: PhysProp
Predicted Water Solubility Not Available Calculated using ALOGPS
Experimental LogP/Hydrophobicity -0.117 Source: PhysProp
Predicted LogP Not Available Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS Not Available Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point 5.73
Mass Spectrum Not Available
MOL File Not Available
SDF File Not Available
PDB File Not Available
Experimental PDB ID 2PE4 Link Image
Experimental PDB File Show
Experimental PDB Structure
Isomeric SMILES Not Available
Canonical SMILES Not Available
Drug Category
  • Anesthetic Adjuvants
  • Permeabilizing Agents
ATC Codes
AHFS Codes Not Available
Indication For increase of absorption and distribution of other injected drugs and for rehydration
Pharmacology Hyaluronidase hydrolyzes hyaluronic acid and increase diffusion of injected drugs, thus facilitating their absorption. Hyaluronidase is used for enhancing absorption and distribution of other injected drugs.
Mechanism of Action Hyaluronidase is a spreading or diffusing substance. It increase the permeability of connective tissue through the hydrolysis of hyaluronic acid. Hyaluronidase hydrolyzes hyaluronic acid by splitting the glucosaminidic bond between C1 of the glucosamine moiety and C4 of glucuronic acid. This temporarily decreases the viscosity of the cellular cement and increases diffusion of injected fluids or of localized transudates or exudates, thus facilitating their absorption.
Absorption Not Available
Toxicity Not Available
Protein Binding Not Available
Biotransformation Not Available
Half Life Not Available
Dosage Forms Not Available
Patient Information Not Available
Contraindications Not Available
Interactions Not Available
Drug Interactions Not Available
Food Interactions Not Available
Pathways Not Available
General References
  1. Drugs.com Link Image
  2. Wikipedia Link Image
  3. RxList Link Image
Organisms Affected
  • Humans and other mammals
Targets
  1. Serum albumin
  2. N-acetylgalactosamine-6-sulfatase
  3. Hyaluronidase PH-20
  4. Transforming growth factor beta-1
  5. Hyaluronidase-2
  6. Hyaluronidase-1
  7. CD44 antigen
Drug Target 1 [top]
Target 1 ID 587
Target 1 Name Serum albumin
Target 1 Synonyms
  1. Serum albumin precursor
Target 1 Gene Name ALB
Target 1 Protein Sequence >Serum albumin precursor
MKWVTFISLLFLFSSAYSRGVFRRDAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQCPF
EDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEP
ERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLF
FAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAV
ARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLK
ECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYAR
RHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFE
QLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVV
LNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALEVDETYVPKEFNAETFTFHADICTL
SEKERQIKKQTALVELVKHKPKATKEQLKAVMDDFAAFVEKCCKADDKETCFAEEGKKLV
AASQAALGL
Target 1 Number of Residues 619
Target 1 Molecular Weight 69367
Target 1 Theoretical pI 6.21
Target 1 GO Classification
Function
transporter activity
carrier activity
Process
physiological process
cellular physiological process
transport
Component
extracellular region
extracellular space
Target 1 General Function Involved in antioxidant activity
Target 1 Specific Function Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • 1-18
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 28590 Link Image
Target 1 UniProtKB/Swiss-Prot ID P02768 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name ALBU_HUMAN Link Image
Target 1 PDB ID 1HA2 Link Image
Target 1 PDB File Show
Target 1 3D Structure
Target 1 Cellular Location
  • Secreted protein
Target 1 Gene Sequence >1830 bp
ATGAAGTGGGTAACCTTTATTTCCCTTCTTTTTCTCTTTAGCTCGGCTTATTCCAGGGGT
GTGTTTCGTCGAGATGCACACAAGAGTGAGGTTGCTCATCGGTTTAAAGATTTGGGAGAA
GAAAATTTCAAAGCCTTGGTGTTGATTGCCTTTGCTCAGTATCTTCAGCAGTGTCCATTT
GAAGATCATGTAAAATTAGTGAATGAAGTAACTGAATTTGCAAAAACATGTGTTGCTGAT
GAGTCAGCTGAAAATTGTGACAAATCACTTCATACCCTTTTTGGAGACAAATTATGCACA
GTTGCAACTCTTCGTGAAACCTATGGTGAAATGGCTGACTGCTGTGCAAAACAAGAACCT
GGGAGAAATGAATGCTTCTTGCAACACAAAGATGACAACCCAAACCTCCCCCGATTGGTG
AGACCAGAGGTTGATGTGATGTGCACTGCTTTTCATGACAATGAAGAGACATTTTTGAAA
AAATACTTATATGAAATTGCCAGAAGACATCCTTACTTTTATGCCCCGGAACTCCTTTTC
TTTGCTAAAAGGTATAAAGCTGCTTTTACAGAATGTTGCCAAGCTGCTGATAAAGCTGCC
TGCCTGTTGCCAAAGCTCGATGAACTTCGGGATGAAGGGAAGGCTTCGTCTGCCAAACAG
AGACTCAAGTGTGCCAGTCTCCAAAAATTTGGAGAAAGAGCTTTCAAAGCATGGGCAGTA
GCTCGCCTGAGCCAGAGATTTCCCAAAGCTGAGTTTGCAGAAGTTTCCAAGTTAGTGACA
GATCTTACCAAAGTCCACACGGAATGCTGCCATGGAGATCTGCTTGAATGTGCTGATGAC
AGGGCGGACCTTGCCAAGTATATCTGTGAAAATCAAGATTCGATCTCCAGTAAACTGAAG
GAATGCTGTGAAAAACCTCTGTTGGAAAAATCCCACTGCATTGCCGAAGTGGAAAATGAT
GAGATGCCTGCTGACTTGCCTTCATTAGCTGCTGATTTTGTTGAAAGTAAGGATGTTTGC
AAAAACTATGCTGAGGCAAAGGATGTCTTCTTGGGCATGTTTTTGTATGAATATGCAAGA
AGGCATCCTGATTACTCTGTCGTGCTGCTGCTGAGACTTGCCAAGACATATGAAACCACT
CTAGAGAAGTGCTGTGCCGCTGCAGATCCTCATGAATGCTATGCCAAAGTGTTCGATGAA
TTTAAACCTCTTGTGGAAGAGCCTCAGAATTTAATCAAACAAAATTGTGAGCTTTTTGAG
CAGCTTGGAGAGTACAAATTCCAGAATGCGCTGTTAGTTCGTTACACCAAGAAAGTACCC
GAAGTGTCAACTCCAACTCTTGTAGAGGTCTCAAGAAACCTAGGAAAAGTGGGCAGCAAA
TGTTGTAAACATCCTGAAGCAAAAAGAATGCCCTGTGCAGAAGACTATCTATCCGTGGTC
CTGAACCAGTTATGTGTGTTGCATGAGAAAACGCCAGTAAGTGACAGAGTCACCAAATGC
TGCACAGAATCCTTGGTGAACAGGCGACCATGCTTTTCAGCTCTGGAAGTCGATGAAACA
TACGTTCCCAAAGAGTTTAATGCTGAAACATTCACCTTCCATGCAGATATATGCACACTT
TCTGAGAAGGAGAGACAAATCAAGAAACAAACTGCACTTGTTGAGCTCGTGAAACACAAG
CCCAAGGCAACAAAAGAGCAACTGAAAGCTGTTATGGATGATTTCGCTGCTTTTGTAGAG
AAGTGCTGCAAGGCTGACGATAAGGAGACCTGCTTTGCCGAGGAGGGTAAAAAACTTGTT
GCTGCAAGTCAAGCTGCCTTAGGCTTATAA
Target 1 GenBank Gene ID
Target 1 GeneCard ID ALB Link Image
Target 1 GenAtlas ID ALB Link Image
Target 1 HGNC ID HGNC:399 Link Image
Target 1 Chromosome Location 4
Target 1 Locus 4q11-q13
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Sugio S, Kashima A, Mochizuki S, Noda M, Kobayashi K: Crystal structure of human serum albumin at 2.5 A resolution. Protein Eng. 1999 Jun;12(6):439-46. [PubMed Link Image]
  2. Bhattacharya AA, Curry S, Franks NP: Binding of the general anesthetics propofol and halothane to human serum albumin. High resolution crystal structures. J Biol Chem. 2000 Dec 8;275(49):38731-8. [PubMed Link Image]
  3. Minchiotti L, Campagnoli M, Rossi A, Cosulich ME, Monti M, Pucci P, Kragh-Hansen U, Granel B, Disdier P, Weiller PJ, Galliano M: A nucleotide insertion and frameshift cause albumin Kenitra, an extended and O-glycosylated mutant of human serum albumin with two additional disulfide bridges. Eur J Biochem. 2001 Jan;268(2):344-52. [PubMed Link Image]
  4. Yu Y, Zhang C, Zhou G, Wu S, Qu X, Wei H, Xing G, Dong C, Zhai Y, Wan J, Ouyang S, Li L, Zhang S, Zhou K, Zhang Y, Wu C, He F: Gene expression profiling in human fetal liver and identification of tissue- and developmental-stage-specific genes through compiled expression profiles and efficient cloning of full-length cDNAs. Genome Res. 2001 Aug;11(8):1392-403. [PubMed Link Image]
  5. Spahr CS, Davis MT, McGinley MD, Robinson JH, Bures EJ, Beierle J, Mort J, Courchesne PL, Chen K, Wahl RC, Yu W, Luethy R, Patterson SD: Towards defining the urinary proteome using liquid chromatography-tandem mass spectrometry. I. Profiling an unfractionated tryptic digest. Proteomics. 2001 Jan;1(1):93-107. [PubMed Link Image]
  6. Petitpas I, Grune T, Bhattacharya AA, Curry S: Crystal structures of human serum albumin complexed with monounsaturated and polyunsaturated fatty acids. J Mol Biol. 2001 Dec 14;314(5):955-60. [PubMed Link Image]
  7. Meloun B, Moravek L, Kostka V: Complete amino acid sequence of human serum albumin. FEBS Lett. 1975 Oct 15;58(1):134-7. [PubMed Link Image]
  8. Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J: Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nat Biotechnol. 2003 May;21(5):566-9. Epub 2003 Mar 31. [PubMed Link Image]
  9. Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. Genome Res. 2003 Oct;13(10):2265-70. Epub 2003 Sep 15. [PubMed Link Image]
  10. Minchiotti L, Galliano M, Stoppini M, Ferri G, Crespeau H, Rochu D, Porta F: Two alloalbumins with identical electrophoretic mobility are produced by differently charged amino acid substitutions. Biochim Biophys Acta. 1992 Mar 12;1119(3):232-8. [PubMed Link Image]
  11. 1518850 Carlson J, Sakamoto Y, Laurell CB, Madison J, Watkins S, Putnam FW: Alloalbuminemia in Sweden: structural study and phenotypic distribution of nine albumin variants. Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):8225-9.
  12. 1630489 He XM, Carter DC: Atomic structure and chemistry of human serum albumin. Nature. 1992 Jul 16;358(6383):209-15.
  13. 1859851 Peach RJ, Brennan SO: Structural characterization of a glycoprotein variant of human serum albumin: albumin Casebrook (494 Asp----Asn). Biochim Biophys Acta. 1991 Jul 26;1097(1):49-54.
  14. 1946412 Madison J, Arai K, Sakamoto Y, Feld RD, Kyle RA, Watkins S, Davis E, Matsuda Y, Amaki I, Putnam FW: Genetic variants of serum albumin in Americans and Japanese. Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9853-7.
  15. 2068071 Watkins S, Madison J, Davis E, Sakamoto Y, Galliano M, Minchiotti L, Putnam FW: A donor splice mutation and a single-base deletion produce two carboxyl-terminal variants of human serum albumin. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):5959-63.
  16. 2104980 Brennan SO, Myles T, Peach RJ, Donaldson D, George PM: Albumin Redhill (-1 Arg, 320 Ala----Thr): a glycoprotein variant of human serum albumin whose precursor has an aberrant signal peptidase cleavage site. Proc Natl Acad Sci U S A. 1990 Jan;87(1):26-30.
  17. 2247440 Galliano M, Minchiotti L, Porta F, Rossi A, Ferri G, Madison J, Watkins S, Putnam FW: Mutations in genetic variants of human serum albumin found in Italy. Proc Natl Acad Sci U S A. 1990 Nov;87(22):8721-5.
  18. 2374930 Carter DC, He XM: Structure of human serum albumin. Science. 1990 Jul 20;249(4966):302-3.
  19. 2404284 Arai K, Madison J, Shimizu A, Putnam FW: Point substitutions in albumin genetic variants from Asia. Proc Natl Acad Sci U S A. 1990 Jan;87(1):497-501.
  20. 2419329 Urano Y, Watanabe K, Sakai M, Tamaoki T: The human albumin gene. Characterization of the 5' and 3' flanking regions and the polymorphic gene transcripts. J Biol Chem. 1986 Mar 5;261(7):3244-51.
  21. 2437111 Carraway RE, Mitra SP, Cochrane DE: Structure of a biologically active neurotensin-related peptide obtained from pepsin-treated albumin(s). J Biol Chem. 1987 May 5;262(13):5968-73.
  22. 2727704 Carter DC, He XM, Munson SH, Twigg PD, Gernert KM, Broom MB, Miller TY: Three-dimensional structure of human serum albumin. Science. 1989 Jun 9;244(4909):1195-8.
  23. 2762316 Arai K, Madison J, Huss K, Ishioka N, Satoh C, Fujita M, Neel JV, Sakurabayashi I, Putnam FW: Point substitutions in Japanese alloalbumins. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6092-6.
  24. 2911589 Arai K, Ishioka N, Huss K, Madison J, Putnam FW: Identical structural changes in inherited albumin variants from different populations. Proc Natl Acad Sci U S A. 1989 Jan;86(2):434-8.
  25. 3009475 Minghetti PP, Ruffner DE, Kuang WJ, Dennison OE, Hawkins JW, Beattie WG, Dugaiczyk A: Molecular structure of the human albumin gene is revealed by nucleotide sequence within q11-22 of chromosome 4. J Biol Chem. 1986 May 25;261(15):6747-57.
  26. 3087352 Mogard MH, Kobayashi R, Chen CF, Lee TD, Reeve JR Jr, Shively JE, Walsh JH: The amino acid sequence of kinetensin, a novel peptide isolated from pepsin-treated human plasma: homology with human serum albumin, neurotensin and angiotensin. Biochem Biophys Res Commun. 1986 May 14;136(3):983-8.
  27. 3474609 Takahashi N, Takahashi Y, Blumberg BS, Putnam FW: Amino acid substitutions in genetic variants of human serum albumin and in sequences inferred from molecular cloning. Proc Natl Acad Sci U S A. 1987 Jul;84(13):4413-7.
  28. 3479777 Takahashi N, Takahashi Y, Isobe T, Putnam FW, Fujita M, Satoh C, Neel JV: Amino acid substitutions in inherited albumin variants from Amerindian and Japanese populations. Proc Natl Acad Sci U S A. 1987 Nov;84(22):8001-5.
  29. 3828358 Brennan SO, Herbert P: Albumin Canterbury (313 Lys----Asn). A point mutation in the second domain of serum albumin. Biochim Biophys Acta. 1987 Apr 8;912(2):191-7.
  30. 6171778 Lawn RM, Adelman J, Bock SC, Franke AE, Houck CM, Najarian RC, Seeburg PH, Wion KL: The sequence of human serum albumin cDNA and its expression in E. coli. Nucleic Acids Res. 1981 Nov 25;9(22):6103-114.
  31. 6275391 Dugaiczyk A, Law SW, Dennison OE: Nucleotide sequence and the encoded amino acids of human serum albumin mRNA. Proc Natl Acad Sci U S A. 1982 Jan;79(1):71-5.
  32. 656055 Jacobsen C: Lysine residue 240 of human serum albumin is involved in high-affinity binding of bilirubin. Biochem J. 1978 May 1;171(2):453-9.
  33. 7852505 Rushbrook JI, Becker E, Schussler GC, Divino CM: Identification of a human serum albumin species associated with familial dysalbuminemic hyperthyroxinemia. J Clin Endocrinol Metab. 1995 Feb;80(2):461-7.
  34. 7895732 Corbett JM, Wheeler CH, Baker CS, Yacoub MH, Dunn MJ: The human myocardial two-dimensional gel protein database: update 1994. Electrophoresis. 1994 Nov;15(11):1459-65.
  35. 7902134 Galliano M, Minchiotti L, Iadarola P, Stoppini M, Giagnoni P, Watkins S, Madison J, Putnam FW: Protein and DNA sequence analysis of a 'private' genetic variant: albumin Ortonovo (Glu-505-->Lys). Biochim Biophys Acta. 1993 Nov 25;1225(1):27-32.
  36. 8022807 Madison J, Galliano M, Watkins S, Minchiotti L, Porta F, Rossi A, Putnam FW: Genetic variants of human serum albumin in Italy: point mutants and a carboxyl-terminal variant. Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6476-80.
  37. 8048949 Sunthornthepvarakul T, Angkeow P, Weiss RE, Hayashi Y, Refetoff S: An identical missense mutation in the albumin gene results in familial dysalbuminemic hyperthyroxinemia in 8 unrelated families. Biochem Biophys Res Commun. 1994 Jul 29;202(2):781-7.
  38. 8347685 Brennan SO, Fellowes AP: Albumin Hawkes Bay; a low level variant caused by loss of a sulphydryl group at position 177. Biochim Biophys Acta. 1993 Aug 4;1182(1):46-50.
  39. 8513793 Minchiotti L, Galliano M, Zapponi MC, Tenni R: The structural characterization and bilirubin-binding properties of albumin Herborn, a [Lys240-->Glu] albumin mutant. Eur J Biochem. 1993 Jun 1;214(2):437-44.
  40. 9329347 Wada N, Chiba H, Shimizu C, Kijima H, Kubo M, Koike T: A novel missense mutation in codon 218 of the albumin gene in a distinct phenotype of familial dysalbuminemic hyperthyroxinemia in a Japanese kindred. J Clin Endocrinol Metab. 1997 Oct;82(10):3246-50.
  41. 955075 Walker JE: Lysine residue 199 of human serum albumin is modified by acetylsalicyclic acid. FEBS Lett. 1976 Jul 15;66(2):173-5.
  42. 9589637 Sunthornthepvarakul T, Likitmaskul S, Ngowngarmratana S, Angsusingha K, Kitvitayasak S, Scherberg NH, Refetoff S: Familial dysalbuminemic hypertriiodothyroninemia: a new, dominantly inherited albumin defect. J Clin Endocrinol Metab. 1998 May;83(5):1448-54.
  43. 9731778 Curry S, Mandelkow H, Brick P, Franks N: Crystal structure of human serum albumin complexed with fatty acid reveals an asymmetric distribution of binding sites. Nat Struct Biol. 1998 Sep;5(9):827-35.
Target 1 Drug References
  1. Maingonnat C, Victor R, Bertrand P, Courel MN, Maunoury R, Delpech B: Activation and inhibition of human cancer cell hyaluronidase by proteins. Anal Biochem. 1999 Mar 1;268(1):30-4. [PubMed Link Image]
  2. Knupfer MM, Poppenborg H, Hotfilder M, Kuhnel K, Wolff JE, Domula M: CD44 expression and hyaluronic acid binding of malignant glioma cells. Clin Exp Metastasis. 1999 Feb;17(1):71-6. [PubMed Link Image]
  3. Parameswaran S, Brown LV, Ibbott GS, Lai-Fook SJ: Effect of concentration and hyaluronidase on albumin diffusion across rabbit mesentery. Microcirculation. 1999 Jun;6(2):117-26. [PubMed Link Image]
  4. de Azeredo LA, Leite SG, Freire DM, Benchetrit LC, Coelho RR: Proteases from actinomycetes interfere in solid media plate assays of hyaluronidase activity. J Microbiol Methods. 2001 Jul;45(3):207-12. [PubMed Link Image]
  5. Li J, Lai-Fook SJ: Effect of hyaluronidase on interstitial pressure response to edema in air-inflated rabbit lung. Respir Physiol. 1992 Aug;89(2):133-46. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 1045
Target 2 Name N-acetylgalactosamine-6-sulfatase
Target 2 Synonyms
  1. Chondroitinase
  2. Chondroitinsulfatase
  3. EC 3.1.6.4
  4. GalNAc6S sulfatase
  5. Galactose-6-sulfate sulfatase
  6. N- acetylgalactosamine-6-sulfate sulfatase
  7. N-acetylgalactosamine-6-sulfatase precursor
Target 2 Gene Name GALNS
Target 2 Protein Sequence >N-acetylgalactosamine-6-sulfatase precursor
MAAVVAATRWWQLLLVLSAAGMGASGAPQPPNILLLLMDDMGWGDLGVYGEPSRETPNLD
RMAAEGLLFPNFYSANPLCSPSRAALLTGRLPIRNGFYTTNAHARNAYTPQEIVGGIPDS
EQLLPELLKKAGYVSKIVGKWHLGHRPQFHPLKHGFDEWFGSPNCHFGPYDNKARPNIPV
YRDWEMVGRYYEEFPINLKTGEANLTQIYLQEALDFIKRQARHHPFFLYWAVDATHAPVY
ASKPFLGTSQRGRYGDAVREIDDSIGKILELLQDLHVADNTFVFFTSDNGAALISAPEQG
GSNGPFLCGKQTTFEGGMREPALAWWPGHVTAGQVSHQLGSIMDLFTTSLALAGLTPPSD
RAIDGLNLLPTLLQGRLMDRPIFYYRGDTLMAATLGQHKAHFWTWTNSWENFRQGIDFCP
GQNVSGVTTHNLEDHTKLPLIFHLGRDPGERFPLSFASAEYQEALSRITSVVQQHQEALV
PAQPQLNVCNWAVMNWAPPGCEKLGKCLTPPESIPKKCLWSH
Target 2 Number of Residues 530
Target 2 Molecular Weight 58027
Target 2 Theoretical pI 6.73
Target 2 GO Classification
Function
catalytic activity
hydrolase activity
hydrolase activity, acting on ester bonds
sulfuric ester hydrolase activity
Process
physiological process
metabolism
Component
Not Available
Target 2 General Function Inorganic ion transport and metabolism
Target 2 Specific Function Hydrolysis of the 6-sulfate groups of the N- acetyl-D-galactosamine 6-sulfate units of chondroitin sulfate and of the D-galactose 6-sulfate units of keratan sulfate
Target 2 Pathways
Name SMPDB Link KEGG Link
Glycosaminoglycan degradation map00531 Link Image
Target 2 Reactions
  • Hydrolysis of the 6-sulfate groups of the N-acetyl-D-galactosamine 6-sulfate units of chondroitin sulfate and of the D-galactose 6-sulfate units of keratan sulfate
Target 2 Pfam Domain Function
Target 2 Signals
  • 1-26
Target 2 Transmembrane Regions
  • None
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 870751 Link Image
Target 2 UniProtKB/Swiss-Prot ID P34059 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name GALNS_HUMAN Link Image
Target 2 PDB ID Not Available
Target 2 Cellular Location
  • Lysosome
Target 2 Gene Sequence >1569 bp
ATGGCGGCGGTTGTCGCGGCGACGAGGTGGTGGCAGCTGTTGCTGGTGCTCAGCGCCGCG
GGGATGGGGGCCTCGGGCGCCCCGCAGCCCCCCAACATCCTGCTCCTGCTCATGGACGAC
ATGGGATGGGGTGACCTCGGGGTGTATGGAGAGCCCTCCAGAGAGACCCCGAATTTGGAC
CGGATGGCTGCAGAAGGGCTGCTTTTCCCAAACTTCTATTCTGCCAACCCTCTGTGCTCG
CCATCGAGGGCGGCACTGCTCACAGGACGGCTACCCATCCGCAATGGCTTCTACACCACC
AACGCCCATGCCAGAAACGCCTACACACCGCAGGAGATTGTGGGCGGCATCCCAGACTCG
GAGCAGCTCCTGCCGGAGCTTCTGAAGAAGGCCGGCTACGTCAGCAAGATTGTCGGCAAG
TGGCATCTGGGTCACAGGCCCCAGTTCCACCCCCTGAAGCACGGATTTGATGAGTGGTTT
GGATCCCCCAACTGCCACTTTGGACCTTATGACAACAAGGCCAGGCCCAACATCCCTGTG
TACAGGGACTGGGAGATGGTTGGCAGATATTATGAAGAATTTCCTATTAATCTGAAGACG
GGGGAAGCCAACCTCACCCAGATCTACCTGCAGGAAGCCCTGGACTTCATTAAGAGACAG
GCACGGCACCACCCCTTTTTCCTCTACTGGGCTGTCGACGCCACGCATGCACCCGTCTAT
GCCTCCAAACCCTTCTTGGGCACCAGTCAGCGAGGGCGGTATGGAGACGCCGTCCGGGAG
ATTGATGACAGCATTGGGAAGATACTGGAGCTCCTCCAAGACCTGCACGTCGCGGACAAC
ACCTTCGTCTTCTTCACGTCGGACAACGGCGCTGCCCTCATTTCCGCCCCCGAACAAGGT
GGCAGCAACGGCCCCTTTCTGTGTGGGAAGCAGACCACGTTTGAAGGAGGGATGAGGGAG
CCTGCCCTCGCATGGTGGCCAGGGCACGTCACTGCAGGCCAGGTGAGCCACCAGCTGGGC
AGCATCATGGACCTCTTCACCACCAGCCTGGCCCTTGCGGGCCTGACGCCGCCCAGCGAC
AGGGCCATTGATGGCCTCAACCTCCTCCCCACCCTCCTGCAGGGCCGGCTGATGGACAGG
CCTATCTTCTATTACCGTGGCGACACGCTGATGGCGGCCACCCTCGGGCAGCACAAGGCT
CACTTCTGGACCTGGACCAACTCCTGGGAGAACTTCAGACAGGGCATTGATTTCTGCCCT
GGGCAGAACGTTTCAGGGGTCACAACTCACAATCTGGAAGACCACACGAAGCTGCCCCTG
ATCTTCCACCTGGGACGGGACCCAGGGGAGAGGTTCCCCCTCAGCTTTGCCAGCGCCGAG
TACCAGGAGGCCCTCAGCAGGATCACCTCGGTCGTCCAGCAGCACCAGGAAGCCTTGGTC
CCCGCGCAGCCCCAGCTCAACGTGTGCAACTGGGCGGTCATGAACTGGGCACCTCCGGGC
TGTGAAAAGTTAGGGAAGTGTCTGACACCTCCAGAATCCATTCCCAAGAAGTGCCTCTGG
TCCCACTAG
Target 2 GenBank Gene ID
Target 2 GeneCard ID GALNS Link Image
Target 2 GenAtlas ID GALNS Link Image
Target 2 HGNC ID HGNC:4122 Link Image
Target 2 Chromosome Location 16
Target 2 Locus 16q24.3
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Fukuda S, Tomatsu S, Masue M, Sukegawa K, Iwata H, Ogawa T, Nakashima Y, Hori T, Yamagishi A, Hanyu Y, et al.: Mucopolysaccharidosis type IVA. N-acetylgalactosamine-6-sulfate sulfatase exonic point mutations in classical Morquio and mild cases. J Clin Invest. 1992 Sep;90(3):1049-53. [PubMed Link Image]
  2. Tomatsu S, Fukuda S, Masue M, Sukegawa K, Fukao T, Yamagishi A, Hori T, Iwata H, Ogawa T, Nakashima Y, et al.: Morquio disease: isolation, characterization and expression of full-length cDNA for human N-acetylgalactosamine-6-sulfate sulfatase. Biochem Biophys Res Commun. 1991 Dec 16;181(2):677-83. [PubMed Link Image]
  3. Tomatsu S, Fukuda S, Cooper A, Wraith JE, Yamada N, Isogai K, Kato Z, Sukegawa K, Kondo N, Suzuki Y, et al.: Two new mutations, Q473X and N487S, in a Caucasian patient with mucopolysaccharidosis IVA (Morquio disease). Hum Mutat. 1995;6(2):195-6. [PubMed Link Image]
  4. Tomatsu S, Fukuda S, Cooper A, Wraith JE, Rezvi GM, Yamagishi A, Yamada N, Kato Z, Isogai K, Sukegawa K, et al.: Mucopolysaccharidosis type IVA: identification of six novel mutations among non-Japanese patients. Hum Mol Genet. 1995 Apr;4(4):741-3. [PubMed Link Image]
  5. Tomatsu S, Fukuda S, Cooper A, Wraith JE, Rezvi GM, Yamagishi A, Yamada N, Kato Z, Isogai K, Sukegawa K, et al.: Mucopolysaccharidosis IVA: identification of a common missense mutation I113F in the N-Acetylgalactosamine-6-sulfate sulfatase gene. Am J Hum Genet. 1995 Sep;57(3):556-63. [PubMed Link Image]
  6. Ogawa T, Tomatsu S, Fukuda S, Yamagishi A, Rezvi GM, Sukegawa K, Kondo N, Suzuki Y, Shimozawa N, Oru T: Mucopolysaccharidosis IVA: screening and identification of mutations of the N-acetylgalactosamine-6-sulfate sulfatase gene. Hum Mol Genet. 1995 Mar;4(3):341-9. [PubMed Link Image]
  7. Morris CP, Guo XH, Apostolou S, Hopwood JJ, Scott HS: Morquio A syndrome: cloning, sequence, and structure of the human N-acetylgalactosamine 6-sulfatase (GALNS) gene. Genomics. 1994 Aug;22(3):652-4. [PubMed Link Image]
  8. Tomatsu S, Fukuda S, Yamagishi A, Cooper A, Wraith JF, Hori T, Kato Z, Yamada N, Isogai K, Sukegawa K, Kondo N, Suzuki Y, Shimozawa N, Orii T: Mucopolysaccharidosis IVA: four new exonic mutations in patients with N-acetylgalactosamine-6-sulfate sulfatase deficiency. Am J Hum Genet. 1996 May;58(5):950-62. [PubMed Link Image]
  9. Cole DE, Fukuda S, Gordon BA, Rip JW, LeCouteur AN, Rupar CA, Tomatsu S, Ogawa T, Sukegawa K, Orii T: Heteroallelic missense mutations of the galactosamine-6-sulfate sulfatase (GALNS) gene in a mild form of Morquio disease (MPS IVA). Am J Med Genet. 1996 Jun 28;63(4):558-65. [PubMed Link Image]
  10. Bunge S, Kleijer WJ, Tylki-Szymanska A, Steglich C, Beck M, Tomatsu S, Fukuda S, Poorthuis BJ, Czartoryska B, Orii T, Gal A: Identification of 31 novel mutations in the N-acetylgalactosamine-6-sulfatase gene reveals excessive allelic heterogeneity among patients with Morquio A syndrome. Hum Mutat. 1997;10(3):223-32. [PubMed Link Image]
  11. 9375852 Tomatsu S, Fukuda S, Cooper A, Wraith JE, Ferreira P, Di Natale P, Tortora P, Fujimoto A, Kato Z, Yamada N, Isogai K, Yamagishi A, Sukegawa K, Suzuki Y, Shimozawa N, Kondo N, Sly WS, Orii T: Fourteen novel mucopolysaccharidosis IVA producing mutations in GALNS gene. Hum Mutat. 1997;10(5):368-75.
  12. 9452036 Tomatsu S, Fukuda S, Cooper A, Wraith JE, Yamagishi A, Kato Z, Yamada N, Isogai K, Sukegawa K, Suzuki Y, Shimozawa N, Kondo N, Orii T: Fifteen polymorphisms in the N-acetylgalactosamine-6-sulfate sulfatase (GALNS) gene: diagnostic implications in Morquio disease. Hum Mutat. 1998;Suppl 1:S42-6.
  13. 9521421 Yamada N, Fukuda S, Tomatsu S, Muller V, Hopwood JJ, Nelson J, Kato Z, Yamagishi A, Sukegawa K, Kondo N, Orii T: Molecular heterogeneity in mucopolysaccharidosis IVA in Australia and Northern Ireland: nine novel mutations including T312S, a common allele that confers a mild phenotype. Hum Mutat. 1998;11(3):202-8.
Target 2 Drug References
  1. Takagaki K, Munakata H, Majima M, Endo M: Enzymatic reconstruction of a hybrid glycosaminoglycan containing 6-sulfated, 4-sulfated, and unsulfated N-acetylgalactosamine. Biochem Biophys Res Commun. 1999 May 19;258(3):741-4. [PubMed Link Image]
  2. Calabro A, Benavides M, Tammi M, Hascall VC, Midura RJ: Microanalysis of enzyme digests of hyaluronan and chondroitin/dermatan sulfate by fluorophore-assisted carbohydrate electrophoresis (FACE). Glycobiology. 2000 Mar;10(3):273-81. [PubMed Link Image]
  3. Hesse L: [Using enzymes in the posterior eye segment. Current status and future possibilities] Ophthalmologe. 2001 Dec;98(12):1176-80. [PubMed Link Image]
  4. Saari H, Tulamo RM, Konttinen YT, Sorsa T: Methylprednisolone acetate induced release of cartilage proteoglycans: determination by high performance liquid chromatography. Ann Rheum Dis. 1992 Feb;51(2):214-9. [PubMed Link Image]
  5. Niv Y, Byrd JC, Ho SB, Dahiya R, Kim YS: Mucin synthesis and secretion in relation to spontaneous differentiation of colon cancer cells in vitro. Int J Cancer. 1992 Jan 2;50(1):147-52. [PubMed Link Image]
Drug Target 3 [top]
Target 3 ID 1136
Target 3 Name Hyaluronidase PH-20
Target 3 Synonyms
  1. EC 3.2.1.35
  2. Hyal-PH20
  3. Hyaluronidase PH-20 precursor
  4. Sperm adhesion molecule 1
  5. Sperm surface protein PH-20
Target 3 Gene Name SPAM1
Target 3 Protein Sequence >Hyaluronidase PH-20 precursor
MGVLKFKHIFFRSFVKSSGVSQIVFTFLLIPCCLTLNFRAPPVIPNVPFLWAWNAPSEFC
LGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISL
QDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLS
LTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHHYKKPGYNGSCFN
VEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPV
FAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGTLSIMRSMKSCLLLDNYMET
ILNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK
PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAFLKPPMETEEPQI
FYNASPSTLSATMFIVSILFLIISSVASL
Target 3 Number of Residues 517
Target 3 Molecular Weight 57848
Target 3 Theoretical pI 7.00
Target 3 GO Classification
Function
catalytic activity
hydrolase activity
hydrolase activity, acting on glycosyl bonds
hydrolase activity, hydrolyzing O-glycosyl compounds
hexosaminidase activity
hyalurononglucosaminidase activity
Process
cellular physiological process
cell organization and biogenesis
membrane organization and biogenesis
membrane fusion
plasma membrane fusion
fusion of sperm to egg plasma membrane
physiological process
metabolism
macromolecule metabolism
carbohydrate metabolism
Component
Not Available
Target 3 General Function Involved in sperm-egg adhesion
Target 3 Specific Function Involved in sperm-egg adhesion. Upon fertilization sperm must first penetrate a layer of cumulus cells that surrounds the egg before reaching the zona pellucida. The cumulus cells are embedded in a matrix containing hyaluronic acid which is formed prior to ovulation. This protein aids in penetrating the layer of cumulus cells by digesting hyaluronic acid
Target 3 Pathways Not Available
Target 3 Reactions
  • Random hydrolysis of 1->4-linkages between N-acetyl-beta-D-glucosamine and D-glucuronate residues in hyaluronate ALL_REAC (other) R07824(G) R07825(G)
Target 3 Pfam Domain Function
Target 3 Signals
  • 1-35
Target 3 Transmembrane Regions
  • None
Target 3 Essentiality Non-Essential
Target 3 GenBank ID Protein Not Available
Target 3 UniProtKB/Swiss-Prot ID P38567 Link Image
Target 3 UniProtKB/Swiss-Prot Entry Name HYALP_HUMAN Link Image
Target 3 PDB ID Not Available
Target 3 Cellular Location
  • Cell membrane
  • GPI-anchor
  • lipid-anchor
Target 3 Gene Sequence Not Available
Target 3 GenBank Gene ID
Target 3 GeneCard ID SPAM1 Link Image
Target 3 GenAtlas ID SPAM1 Link Image
Target 3 HGNC ID HGNC:11217 Link Image
Target 3 Chromosome Location 7
Target 3 Locus 7q31.3
Target 3 SNPs SNPJam Report Link Image
Target 3 General References
  1. Hillier LW, Fulton RS, Fulton LA, Graves TA, Pepin KH, Wagner-McPherson C, Layman D, Maas J, Jaeger S, Walker R, Wylie K, Sekhon M, Becker MC, O'Laughlin MD, Schaller ME, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Cordes M, Du H, Sun H, Edwards J, Bradshaw-Cordum H, Ali J, Andrews S, Isak A, Vanbrunt A, Nguyen C, Du F, Lamar B, Courtney L, Kalicki J, Ozersky P, Bielicki L, Scott K, Holmes A, Harkins R, Harris A, Strong CM, Hou S, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Leonard S, Rohlfing T, Rock SM, Tin-Wollam AM, Abbott A, Minx P, Maupin R, Strowmatt C, Latreille P, Miller N, Johnson D, Murray J, Woessner JP, Wendl MC, Yang SP, Schultz BR, Wallis JW, Spieth J, Bieri TA, Nelson JO, Berkowicz N, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Bedell JA, Mardis ER, Clifton SW, Chissoe SL, Marra MA, Raymond C, Haugen E, Gillett W, Zhou Y, James R, Phelps K, Iadanoto S, Bubb K, Simms E, Levy R, Clendenning J, Kaul R, Kent WJ, Furey TS, Baertsch RA, Brent MR, Keibler E, Flicek P, Bork P, Suyama M, Bailey JA, Portnoy ME, Torrents D, Chinwalla AT, Gish WR, Eddy SR, McPherson JD, Olson MV, Eichler EE, Green ED, Waterston RH, Wilson RK: The DNA sequence of human chromosome 7. Nature. 2003 Jul 10;424(6945):157-64. [PubMed Link Image]
  2. Lin Y, Kimmel LH, Myles DG, Primakoff P: Molecular cloning of the human and monkey sperm surface protein PH-20. Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10071-5. [PubMed Link Image]
  3. Gmachl M, Sagan S, Ketter S, Kreil G: The human sperm protein PH-20 has hyaluronidase activity. FEBS Lett. 1993 Dec 28;336(3):545-8. [PubMed Link Image]
  4. Jones MH, Davey PM, Aplin H, Affara NA: Expression analysis, genomic structure, and mapping to 7q31 of the human sperm adhesion molecule gene SPAM1. Genomics. 1995 Oct 10;29(3):796-800. [PubMed Link Image]
Target 3 Drug References
  1. Csoka AB, Scherer SW, Stern R: Expression analysis of six paralogous human hyaluronidase genes clustered on chromosomes 3p21 and 7q31. Genomics. 1999 Sep 15;60(3):356-61. [PubMed Link Image]
  2. Deng X, He Y, Martin-Deleon PA: Mouse Spam1 (PH-20): evidence for its expression in the epididymis and for a new category of spermatogenic-expressed genes. J Androl. 2000 Nov-Dec;21(6):822-32. [PubMed Link Image]
  3. Cherr GN, Yudin AI, Overstreet JW: The dual functions of GPI-anchored PH-20: hyaluronidase and intracellular signaling. Matrix Biol. 2001 Dec;20(8):515-25. [PubMed Link Image]
  4. Patel S, Turner PR, Stubberfield C, Barry E, Rohlff CR, Stamps A, McKenzie E, Young K, Tyson K, Terrett J, Box G, Eccles S, Page MJ: Hyaluronidase gene profiling and role of hyal-1 overexpression in an orthotopic model of prostate cancer. Int J Cancer. 2002 Feb 1;97(4):416-24. [PubMed Link Image]
  5. Nicoll SB, Barak O, Csoka AB, Bhatnagar RS, Stern R: Hyaluronidases and CD44 undergo differential modulation during chondrogenesis. Biochem Biophys Res Commun. 2002 Apr 12;292(4):819-25. [PubMed Link Image]
Drug Target 4 [top]
Target 4 ID 1389
Target 4 Name Transforming growth factor beta-1
Target 4 Synonyms
  1. TGF-beta-1
  2. Transforming growth factor beta-1 precursor
Target 4 Gene Name TGFB1
Target 4 Protein Sequence >Transforming growth factor beta-1 precursor
MPPSGLRLLLLLLPLLWLLVLTPGRPAAGLSTCKTIDMELVKRKRIEAIRGQILSKLRLA
SPPSQGEVPPGPLPEAVLALYNSTRDRVAGESAEPEPEPEADYYAKEVTRVLMVETHNEI
YDKFKQSTHSIYMFFNTSELREAVPEPVLLSRAELRLLRLKLKVEQHVELYQKYSNNSWR
YLSNRLLAPSDSPEWLSFDVTGVVRQWLSRGGEIEGFRLSAHCSCDSRDNTLQVDINGFT
TGRRGDLATIHGMNRPFLLLMATPLERAQHLQSSRHRRALDTNYCFSSTEKNCCVRQLYI
DFRKDLGWKWIHEPKGYHANFCLGPCPYIWSLDTQYSKVLALYNQHNPGASAAPCCVPQA
LEPLPIVYYVGRKPKVEQLSNMIVRSCKCS
Target 4 Number of Residues 396
Target 4 Molecular Weight 44342
Target 4 Theoretical pI 8.63
Target 4 GO Classification
Function
growth factor activity
signal transducer activity
receptor binding
transforming growth factor beta receptor binding
Process
growth
cell growth
Component
Not Available
Target 4 General Function Involved in transforming growth factor beta receptor binding
Target 4 Specific Function Multifunctional protein that control proliferation, differentiation, and other functions in many cell types. Many cells synthesize TGFB1 and essentially all of them have specific receptors for this protein. It regulates the actions of many other growth factors and determines a positive or negative direction of their effects. It plays an important role in bone remodelling. It is a potent stimulator of osteoblastic bone formation, causing chemotaxis, proliferation and differentiation in committed osteoblasts
Target 4 Pathways Not Available
Target 4 Reactions Not Available
Target 4 Pfam Domain Function
Target 4 Signals
  • 1-29
Target 4 Transmembrane Regions
  • None
Target 4 Essentiality Non-Essential
Target 4 GenBank ID Protein 1212989 Link Image
Target 4 UniProtKB/Swiss-Prot ID P01137 Link Image
Target 4 UniProtKB/Swiss-Prot Entry Name TGFB1_HUMAN Link Image
Target 4 PDB ID 1KLD Link Image
Target 4 PDB File Show
Target 4 3D Structure
Target 4 Cellular Location
  • Secreted protein
Target 4 Gene Sequence >1173 bp
ATGCCGCCCTCCGGGCTGCGGCTGCTGCTGCTGCTGCTACCGCTGCTGTGGCTACTGGTG
CTGACGCCTGGCCGGCCGGCCGCGGGACTATCCACCTGCAAGACTATCGACATGGAGCTG
GTGAAGCGGAAGCGCATCGAGGCCATCCGCGGCCAGATCCTGTCCAAGCTGCGGCTCGCC
AGCCCCCCGAGCCAGGGGGAGGTGCCGCCCGGCCCGCTGCCCGAGGCCGTGCTCGCCCTG
TACAACAGCACCCGCGACCGGGTGGCCGGGGAGAGTGCAGAACCGGAGCCCGAGCCTGAG
GCCGACTACTACGCCAAGGAGGTCACCCGCGTGCTAATGGTGGAAACCCACAACGAAATC
TATGACAAGTTCAAGCAGAGTACACACAGCATATATATGTTCTTCAACACATCAGAGCTC
CGAGAAGCGGTACCTGAACCCGTGTTGCTCTCCCGGGCAGAGCTGCGTCTGCTGAGGCTC
AAGTTAAAAGTGGAGCAGCACGTGGAGCTGTACCAGAAATACAGCAACAATTCCTGGCGA
TACCTCAGCAACCGGCTGCTGGCACCCAGCGACTCGCCAGAGTGGTTATCTTTTGATGTC
ACCGGAGTTGTGCGGCAGTGGTTGAGCCGTGGAGGGGAAATTGAGGGCTTTCGCCTTAGC
GCCCACTGCTCCTGTGACAGCAGGGATAACACACTGCAAGTGGACATCAACGGGTTCACT
ACCGGCCGCCGAGGTGACCTGGCCACCATTCATGGCATGAACCGGCCTTTCCTGCTTCTC
ATGGCCACCCCGCTGGAGAGGGCCCAGCATCTGCAAAGCTCCCGGCACCGCCGAGCCCTG
GACACCAACTATTGCTTCAGCTCCACGGAGAAGAACTGCTGCGTGCGGCAGCTGTACATT
GACTTCCGCAAGGACCTCGGCTGGAAGTGGATCCACGAGCCCAAGGGCTACCATGCCAAC
TTCTGCCTCGGGCCCTGCCCCTACATTTGGAGCCTGGACACGCAGTACAGCAAGGTCCTG
GCCCTGTACAACCAGCATAACCCGGGCGCCTCGGCGGCGCCGTGCTGCGTGCCGCAGGCG
CTGGAGCCGCTGCCCATCGTGTACTACGTGGGCCGCAAGCCCAAGGTGGAGCAGCTGTCC
AACATGATCGTGCGCTCCTGCAAGTGCAGCTAG
Target 4 GenBank Gene ID
Target 4 GeneCard ID TGFB1 Link Image
Target 4 GenAtlas ID TGFB1 Link Image
Target 4 HGNC ID HGNC:11766 Link Image
Target 4 Chromosome Location 19
Target 4 Locus 19q13.2|19q13.1
Target 4 SNPs SNPJam Report Link Image
Target 4 General References
  1. Kinoshita A, Saito T, Tomita H, Makita Y, Yoshida K, Ghadami M, Yamada K, Kondo S, Ikegawa S, Nishimura G, Fukushima Y, Nakagomi T, Saito H, Sugimoto T, Kamegaya M, Hisa K, Murray JC, Taniguchi N, Niikawa N, Yoshiura K: Domain-specific mutations in TGFB1 result in Camurati-Engelmann disease. Nat Genet. 2000 Sep;26(1):19-20. [PubMed Link Image]
  2. Janssens K, Gershoni-Baruch R, Guanabens N, Migone N, Ralston S, Bonduelle M, Lissens W, Van Maldergem L, Vanhoenacker F, Verbruggen L, Van Hul W: Mutations in the gene encoding the latency-associated peptide of TGF-beta 1 cause Camurati-Engelmann disease. Nat Genet. 2000 Nov;26(3):273-5. [PubMed Link Image]
  3. Shur I, Lokiec F, Bleiberg I, Benayahu D: Differential gene expression of cultured human osteoblasts. J Cell Biochem. 2001;83(4):547-53. [PubMed Link Image]
  4. Watanabe Y, Kinoshita A, Yamada T, Ohta T, Kishino T, Matsumoto N, Ishikawa M, Niikawa N, Yoshiura K: A catalog of 106 single-nucleotide polymorphisms (SNPs) and 11 other types of variations in genes for transforming growth factor-beta1 (TGF-beta1) and its signaling pathway. J Hum Genet. 2002;47(9):478-83. [PubMed Link Image]
  5. Janssens K, ten Dijke P, Ralston SH, Bergmann C, Van Hul W: Transforming growth factor-beta 1 mutations in Camurati-Engelmann disease lead to increased signaling by altering either activation or secretion of the mutant protein. J Biol Chem. 2003 Feb 28;278(9):7718-24. Epub 2002 Dec 18. [PubMed Link Image]
  6. McGowan NW, MacPherson H, Janssens K, Van Hul W, Frith JC, Fraser WD, Ralston SH, Helfrich MH: A mutation affecting the latency-associated peptide of TGFbeta1 in Camurati-Engelmann disease enhances osteoclast formation in vitro. J Clin Endocrinol Metab. 2003 Jul;88(7):3321-6. [PubMed Link Image]
  7. Massague J, Like B: Cellular receptors for type beta transforming growth factor. Ligand binding and affinity labeling in human and rodent cell lines. J Biol Chem. 1985 Mar 10;260(5):2636-45. [PubMed Link Image]
  8. Miyazono K, Hellman U, Wernstedt C, Heldin CH: Latent high molecular weight complex of transforming growth factor beta 1. Purification from human platelets and structural characterization. J Biol Chem. 1988 May 5;263(13):6407-15. [PubMed Link Image]
  9. Derynck R, Rhee L, Chen EY, Van Tilburg A: Intron-exon structure of the human transforming growth factor-beta precursor gene. Nucleic Acids Res. 1987 Apr 10;15(7):3188-9. [PubMed Link Image]
  10. Derynck R, Jarrett JA, Chen EY, Eaton DH, Bell JR, Assoian RK, Roberts AB, Sporn MB, Goeddel DV: Human transforming growth factor-beta complementary DNA sequence and expression in normal and transformed cells. Nature. 1985 Aug 22-28;316(6030):701-5. [PubMed Link Image]
  11. 8424942 Archer SJ, Bax A, Roberts AB, Sporn MB, Ogawa Y, Piez KA, Weatherbee JA, Tsang ML, Lucas R, Zheng BL, et al.: Transforming growth factor beta 1: NMR signal assignments of the recombinant protein expressed and isotopically enriched using Chinese hamster ovary cells. Biochemistry. 1993 Feb 2;32(4):1152-63.
  12. 8424943 Archer SJ, Bax A, Roberts AB, Sporn MB, Ogawa Y, Piez KA, Weatherbee JA, Tsang ML, Lucas R, Zheng BL, et al.: Transforming growth factor beta 1: secondary structure as determined by heteronuclear magnetic resonance spectroscopy. Biochemistry. 1993 Feb 2;32(4):1164-71.
  13. 8471846 Bourdrel L, Lin CH, Lauren SL, Elmore RH, Sugarman BJ, Hu S, Westcott KR: Recombinant human transforming growth factor-beta 1: expression by Chinese hamster ovary cells, isolation, and characterization. Protein Expr Purif. 1993 Apr;4(2):130-40.
  14. 8679613 Hinck AP, Archer SJ, Qian SW, Roberts AB, Sporn MB, Weatherbee JA, Tsang ML, Lucas R, Zhang BL, Wenker J, Torchia DA: Transforming growth factor beta 1: three-dimensional structure in solution and comparison with the X-ray structure of transforming growth factor beta 2. Biochemistry. 1996 Jul 2;35(26):8517-34.
  15. 9150447 Munger JS, Harpel JG, Gleizes PE, Mazzieri R, Nunes I, Rifkin DB: Latent transforming growth factor-beta: structural features and mechanisms of activation. Kidney Int. 1997 May;51(5):1376-82.
  16. 9783545 Yamada Y, Miyauchi A, Goto J, Takagi Y, Okuizumi H, Kanematsu M, Hase M, Takai H, Harada A, Ikeda K: Association of a polymorphism of the transforming growth factor-beta1 gene with genetic susceptibility to osteoporosis in postmenopausal Japanese women. J Bone Miner Res. 1998 Oct;13(10):1569-76.
Target 4 Drug References
  1. Chang NS: Hyaluronidase activation of c-Jun N-terminal kinase is necessary for protection of L929 fibrosarcoma cells from staurosporine-mediated cell death. Biochem Biophys Res Commun. 2001 May 4;283(2):278-86. [PubMed Link Image]
  2. Locci P, Marinucci L, Lilli C, Martinese D, Becchetti E: Transforming growth factor beta 1-hyaluronic acid interaction. Cell Tissue Res. 1995 Aug;281(2):317-24. [PubMed Link Image]
  3. Chang NS: Hyaluronidase enhancement of TNF-mediated cell death is reversed by TGF-beta 1. Am J Physiol. 1997 Dec;273(6 Pt 1):C1987-94. [PubMed Link Image]
  4. Chang NS: Transforming growth factor-beta protection of cancer cells against tumor necrosis factor cytotoxicity is counteracted by hyaluronidase (review). Int J Mol Med. 1998 Dec;2(6):653-9. [PubMed Link Image]
Drug Target 5 [top]
Target 5 ID 1668
Target 5 Name Hyaluronidase-2
Target 5 Synonyms
  1. EC 3.2.1.35
  2. Hyal-2
  3. Hyaluronidase-2 precursor
  4. Hyaluronoglucosaminidase-2
  5. LUCA-2
Target 5 Gene Name HYAL2
Target 5 Protein Sequence >Hyaluronidase-2 precursor
MRAGPGPTVTLALVLAVAWAMELKPTAPPIFTGRPFVVAWDVPTQDCGPRLKVPLDLNAF
DVQASPNEGFVNQNITIFYRDRLGLYPRFDSAGRSVHGGVPQNVSLWAHRKMLQKRVEHY
IRTQESAGLAVIDWEDWRPVWVRNWQDKDVYRRLSRQLVASRHPDWPPDRIVKQAQYEFE
FAAQQFMLETLRYVKAVRPRHLWGFYLFPDCYNHDYVQNWESYTGRCPDVEVARNDQLAW
LWAESTALFPSVYLDETLASSRHGRNFVSFRVQEALRVARTHHANHALPVYVFTRPTYSR
RLTGLSEMDLISTIGESAALGAAGVILWGDAGYTTSTETCQYLKDYLTRLLVPYVVNVSW
ATQYCSRAQCHGHGRCVRRNPSASTFLHLSTNSFRLVPGHAPGEPQLRPVGELSWADIDH
LQTHFRCQCYLGWSGEQCQWDHRQAAGGASEAWAGSHLTSLLALAALAFTWTL
Target 5 Number of Residues 480
Target 5 Molecular Weight 53844
Target 5 Theoretical pI 8.27
Target 5 GO Classification
Function
catalytic activity
hydrolase activity
hydrolase activity, acting on glycosyl bonds
hydrolase activity, hydrolyzing O-glycosyl compounds
hexosaminidase activity
hyalurononglucosaminidase activity
Process
physiological process
metabolism
macromolecule metabolism
carbohydrate metabolism
Component
Not Available
Target 5 General Function Involved in hyalurononglucosaminidase activity
Target 5 Specific Function Hydrolyzes high molecular weight hyaluronic acid to produce an intermediate-sized product which is further hydrolyzed by sperm hyaluronidase to give small oligosaccharides. Displays very low levels of activity. Associates with and negatively regulates MST1R
Target 5 Pathways Not Available
Target 5 Reactions
  • Random hydrolysis of 1->4-linkages between N-acetyl-beta-D-glucosamine and D-glucuronate residues in hyaluronate ALL_REAC (other) R07824(G) R07825(G)
Target 5 Pfam Domain Function
Target 5 Signals
  • 1-20
Target 5 Transmembrane Regions
  • None
Target 5 Essentiality Non-Essential
Target 5 GenBank ID Protein 4378959 Link Image
Target 5 UniProtKB/Swiss-Prot ID Q12891 Link Image
Target 5 UniProtKB/Swiss-Prot Entry Name HYAL2_HUMAN Link Image
Target 5 PDB ID Not Available
Target 5 Cellular Location
  • Cell membrane
  • GPI-anchor
  • lipid-anchor
Target 5 Gene Sequence >1416 bp
ATGCGGGCAGGCCCAGGCCCCACCGTTACATTGGCCCTGGTGCTGGCGGTGGCATGGGCC
ATGGAGCTCAAGCCCACAGCACCACCCATCTTCACTGGCCGGCCCTTTGTGGTAGCGTGG
GACGTGCCCACACAGGACTGTGGCCCACGCCTCAAGGTGCCACTGGACCTGAATGCCTTT
GATGTGCAGGCCTCACCTAATGAGGGTTTTGTGAACCAGAATATTACCATCTTCTACCGC
GACCGTCTAGGCCTGTATCCACGCTTCGATTCTGCCGGAAGGTCTGTGCATGGTGGTGTG
CCACAGAATGTCAGCCTTTGGGCACACCGGAAGATGCTGCAGAAACGTGTGGAGCACTAC
ATTCGGACACAGGAGTCTGCGGGGCTGGCGGTCATCGACTGGGAGGACTGGCGACCTGTG
TGGGTGCGCAACTGGCAGGACAAAGATGTGTATCGCCGGTTATCACGCCAGCTAGTGGCC
AGTCGTCACCCTGACTGGCCTCCAGACCGCATAGTCAAACAGGCACAATATGAGTTTGAG
TTCGCAGCACAGCAGTTCATGCTGGAGACACTGCGTTATGTCAAGGCAGTGCGGCCCCGG
CACCTCTGGGGCTTCTACCTCTTTCCTGACTGCTACAATCATGATTATGTGCAGAACTGG
GAGAGCTACACAGGCCGCTGCCCTGATGTTGAGGTGGCCCGCAATGACCAGCTGGCCTGG
CTGTGGGCTGAGAGCACGGCCCTCTTCCCGTCTGTCTACCTGGACGAGACACTTGCTTCC
GCCCTCCATGGCCGCAACTTTGTGAGCTTCCGTGTTCAGGAGGCCCTTCGTGTGGCTCGC
ACCCACCATGCCAACCATGCACTCCCAGTCTACGTCTTCACACGACCCACCTACAGCCGC
TGCACGGGGCTTAGTGAGATGGACCTCATCTCTACCATTGGCGAGAGTGCGGCCCTGGGC
GCAGCTGGTGTCATCCTCTGGGGTGACGCGGGGTACACCACAAGCACGGAGACCTGCCAG
TACCTCAAAGATTACCTGACACGGCTGCTGGTCCCCTACGTGGTCAATGTGTCCTGGGCC
ACCCAATATTGCAGCCGGGCCCAGTGCCATGGCCATGGCTGTGTGCCCGGCAACCCCAGT
GCCAGTACCTTCCTGCATCTCAGCACCAACAGTTTCCGCCTAGTGCCTGGCCATGCACCT
GGTGAACCCCAGCTGCGACCTGTGGGGGAGCTCAGTTGGGCCGACATTGACCACCTGCAG
ACACACTTCCGCTGCCAGTGCTACTTGGGCTGGAGTGGTGAGCAATGCCAGTGGGACCAT
AGGCAGGCAGCTGGAGGTGCCAACGAGGCCTGGGCTGGGTCCCACCTCACCAGTCTGCTG
GCTCTGGCAGCCCTGGCCTTTACCTGGACCTTGTAG
Target 5 GenBank Gene ID
Target 5 GeneCard ID HYAL2 Link Image
Target 5 GenAtlas ID HYAL2 Link Image
Target 5 HGNC ID HGNC:5321 Link Image
Target 5 Chromosome Location 3
Target 5 Locus 3p21.3
Target 5 SNPs SNPJam Report Link Image
Target 5 General References
  1. Rai SK, Duh FM, Vigdorovich V, Danilkovitch-Miagkova A, Lerman MI, Miller AD: Candidate tumor suppressor HYAL2 is a glycosylphosphatidylinositol (GPI)-anchored cell-surface receptor for jaagsiekte sheep retrovirus, the envelope protein of which mediates oncogenic transformation. Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4443-8. [PubMed Link Image]
  2. Lepperdinger G, Mullegger J, Kreil G: Hyal2--less active, but more versatile? Matrix Biol. 2001 Dec;20(8):509-14. [PubMed Link Image]
  3. Lepperdinger G, Strobl B, Kreil G: HYAL2, a human gene expressed in many cells, encodes a lysosomal hyaluronidase with a novel type of specificity. J Biol Chem. 1998 Aug 28;273(35):22466-70. [PubMed Link Image]
Target 5 Drug References
  1. Csoka AB, Scherer SW, Stern R: Expression analysis of six paralogous human hyaluronidase genes clustered on chromosomes 3p21 and 7q31. Genomics. 1999 Sep 15;60(3):356-61. [PubMed Link Image]
  2. Rai SK, Duh FM, Vigdorovich V, Danilkovitch-Miagkova A, Lerman MI, Miller AD: Candidate tumor suppressor HYAL2 is a glycosylphosphatidylinositol (GPI)-anchored cell-surface receptor for jaagsiekte sheep retrovirus, the envelope protein of which mediates oncogenic transformation. Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4443-8. [PubMed Link Image]
  3. Csoka AB, Frost GI, Stern R: The six hyaluronidase-like genes in the human and mouse genomes. Matrix Biol. 2001 Dec;20(8):499-508. [PubMed Link Image]
  4. Mullegger J, Lepperdinger G: Degradation of hyaluronan by a Hyal2-type hyaluronidase affects pattern formation of vitelline vessels during embryogenesis of Xenopus laevis. Mech Dev. 2002 Feb;111(1-2):25-35. [PubMed Link Image]
  5. Chang NS: Transforming growth factor-beta1 blocks the enhancement of tumor necrosis factor cytotoxicity by hyaluronidase Hyal-2 in L929 fibroblasts. BMC Cell Biol. 2002 Apr 3;3:8. [PubMed Link Image]
Drug Target 6 [top]
Target 6 ID 1858
Target 6 Name Hyaluronidase-1
Target 6 Synonyms
  1. EC 3.2.1.35
  2. Hyal-1
  3. Hyaluronidase-1 precursor
  4. Hyaluronoglucosaminidase-1
  5. LUCA-1
Target 6 Gene Name HYAL1
Target 6 Protein Sequence >Hyaluronidase-1 precursor
MAAHLLPICALFLTLLDMAQGFRGPLLPNRPFTTVWNANTQWCLERHGVDVDVSVFDVVA
NPGQTFRGPDMTIFYSSQLGTYPYYTPTGEPVFGGLPQNASLIAHLARTFQDILAAIPAP
DFSGLAVIDWEAWRPRWAFNWDTKDIYRQRSRALVQAQHPDWPAPQVEAVAQDQFQGAAR
AWMAGTLQLGRALRPRGLWGFYGFPDCYNYDFLSPNYTGQCPSGIRAQNDQLGWLWGQSR
ALYPSIYMPAVLEGTGKSQMYVQHRVAEAFRVAVAAGDPNLPVLPYVQIFYDTTNHFLPL
DELEHSLGESAAQGAAGVVLWVSWENTRTKESCQAIKEYMDTTLGPFILNVTSGALLCSQ
ALCSGHGRCVRRTSHPKALLLLNPASFSIQLTPGGGPLSLRGALSLEDQAQMAVEFKCRC
YPGWQAPWCERKSMW
Target 6 Number of Residues 442
Target 6 Molecular Weight 48368
Target 6 Theoretical pI 6.77
Target 6 GO Classification
Function
catalytic activity
hydrolase activity
hydrolase activity, acting on glycosyl bonds
hydrolase activity, hydrolyzing O-glycosyl compounds
hexosaminidase activity
hyalurononglucosaminidase activity
Process
physiological process
metabolism
macromolecule metabolism
carbohydrate metabolism
Component
Not Available
Target 6 General Function Involved in hyalurononglucosaminidase activity
Target 6 Specific Function May have a role in promoting tumor progression. May block the TGFB1-enhanced cell growth
Target 6 Pathways Not Available
Target 6 Reactions
  • Random hydrolysis of 1->4-linkages between N-acetyl-beta-D-glucosamine and D-glucuronate residues in hyaluronate ALL_REAC (other) R07824(G) R07825(G)
Target 6 Pfam Domain Function
Target 6 Signals
  • 1-21
Target 6 Transmembrane Regions
  • None
Target 6 Essentiality Non-Essential
Target 6 GenBank ID Protein 9989698 Link Image
Target 6 UniProtKB/Swiss-Prot ID Q12794 Link Image
Target 6 UniProtKB/Swiss-Prot Entry Name HYAL1_HUMAN Link Image
Target 6 PDB ID Not Available
Target 6 Cellular Location
  • Secreted protein. Lysosome
Target 6 Gene Sequence >1308 bp
ATGGCAGCCCACCTGCTTCCCATCTGCGCCCTCTTCCTGACCTTACTCGATATGGCCCAA
GGCTTTAGGGGCCCCTTGCTACCCAACCGGCCCTTCACCACCGTCTGGAATGCAAACACC
CAGTGGTGCCTGGAGAGGCACGGTGTGGACGTGGATGTCAGTGTCTTCGATGTGGTAGCC
AACCCAGGGCAGACCTTCCGCGGCCCTGACATGACAATTTTCTATAGCTCCCAGCTGGGC
ACCTACCCCTACTACACGCCCACTGGGGAGCCTGTGTTTGGTGGTCTGCCCCAGAATGCC
AGCCTGATTGCCCACCTGGCCCGCACATTCCAGGACATCCTGGCTGCCATACCTGCTCCT
GACTTCTCAGGGCTGGCAGTCATCGACTGGGAGGCATGGCGCCCACGCTGGGCCTTCAAC
TGGGACACCAAGGACATTTACCGGCAGCGCTCACGGGCACTGGTACAGGCACAGCACCCT
GATTGGCCAGCTCCTCAGGTGGAGGCAGTAGCCCAGGACCAGTTCCAGGGAGCTGCACGG
GCCTGGATGGCAGGCACCCTCCAGCTGGGGCGGGCACTGCGTCCTCGCGGCCTCTGGGGC
TTCTATGGCTTCCCTGACTGCTACAACTATGACTTTCTAAGCCCCAACTACACCGGCCAG
TGCCCATCAGGCATCCGTGCCCAAAATGACCAGCTAGGGTGGCTGTGGGGCCAGAGCCGT
GCCCTCTATCCCAGCATCTACATGCCCGCAGTGCTGGAGGGCACAGGGAAGTCACAGATG
TATGTGCAACACCGTGTGGCCGAGGCATTCCGTGTGGCTGTGGCTGCTGGTGACCCCAAT
CTGCCGGTGCTGCCCTATGTCCAGATCTTCTATGACACGACAAACCACTTTCTGCCCCTG
GATGAGCTGGAGCACAGCCTGGGGGAGAGTGCGGCCCAGGGGGCAGCTGGAGTGGTGCTC
TGGGTGAGCTGGGAAAATACAAGAACCAAGGAATCATGTCAGGCCATCAAGGAGTATATG
GACACTACACTGGGGCCCTTCATCCTGAACGTGACCAGTGGGGCCCTTCTCTGCAGTCAA
GCCCTGTGCTCCGGCCATGGCCGCTGTGTCCGCCGCACCAGCCACCCCAAAGCCCTCCTC
CTCCTTAACCCTGCCAGTTTCTCCATCCAGCTCACGCCTGGTGGTGGGCCCCTGAGCCTG
CGGGGTGCCCTCTCACTTGAAGATCAGGCACAGATGGCTGTGGAGTTCAAATGTCGATGC
TACCCTGGCTGGCAGGCACCGTGGTGTGAGCGGAAGAGCATGTGGTGA
Target 6 GenBank Gene ID
Target 6 GeneCard ID HYAL1 Link Image
Target 6 GenAtlas ID HYAL1 Link Image
Target 6 HGNC ID HGNC:5320 Link Image
Target 6 Chromosome Location 3
Target 6 Locus 3p21.3-p21.2
Target 6 SNPs SNPJam Report Link Image
Target 6 General References
  1. Triggs-Raine B, Salo TJ, Zhang H, Wicklow BA, Natowicz MR: Mutations in HYAL1, a member of a tandemly distributed multigene family encoding disparate hyaluronidase activities, cause a newly described lysosomal disorder, mucopolysaccharidosis IX. Proc Natl Acad Sci U S A. 1999 May 25;96(11):6296-300. [PubMed Link Image]
  2. Frost GI, Mohapatra G, Wong TM, Csoka AB, Gray JW, Stern R: HYAL1LUCA-1, a candidate tumor suppressor gene on chromosome 3p21.3, is inactivated in head and neck squamous cell carcinomas by aberrant splicing of pre-mRNA. Oncogene. 2000 Feb 17;19(7):870-7. [PubMed Link Image]
  3. Lokeshwar VB, Schroeder GL, Carey RI, Soloway MS, Iida N: Regulation of hyaluronidase activity by alternative mRNA splicing. J Biol Chem. 2002 Sep 13;277(37):33654-63. Epub 2002 Jun 25. [PubMed Link Image]
  4. Wei MH, Latif F, Bader S, Kashuba V, Chen JY, Duh FM, Sekido Y, Lee CC, Geil L, Kuzmin I, Zabarovsky E, Klein G, Zbar B, Minna JD, Lerman MI: Construction of a 600-kilobase cosmid clone contig and generation of a transcriptional map surrounding the lung cancer tumor suppressor gene (TSG) locus on human chromosome 3p21.3: progress toward the isolation of a lung cancer TSG. Cancer Res. 1996 Apr 1;56(7):1487-92. [PubMed Link Image]
  5. Frost GI, Csoka AB, Wong T, Stern R: Purification, cloning, and expression of human plasma hyaluronidase. Biochem Biophys Res Commun. 1997 Jul 9;236(1):10-5. [PubMed Link Image]
Target 6 Drug References
  1. Csoka AB, Scherer SW, Stern R: Expression analysis of six paralogous human hyaluronidase genes clustered on chromosomes 3p21 and 7q31. Genomics. 1999 Sep 15;60(3):356-61. [PubMed Link Image]
  2. Reitinger S, Mullegger J, Lepperdinger G: Xenopus kidney hyaluronidase-1 (XKH1), a novel type of membrane-bound hyaluronidase solely degrades hyaluronan at neutral pH. FEBS Lett. 2001 Sep 14;505(2):213-6. [PubMed Link Image]
  3. Shuttleworth TL, Wilson MD, Wicklow BA, Wilkins JA, Triggs-Raine BL: Characterization of the murine hyaluronidase gene region reveals complex organization and cotranscription of Hyal1 with downstream genes, Fus2 and Hyal3. J Biol Chem. 2002 Jun 21;277(25):23008-18. Epub 2002 Apr 2. [PubMed Link Image]
  4. Lokeshwar VB, Cerwinka WH, Isoyama T, Lokeshwar BL: HYAL1 hyaluronidase in prostate cancer: a tumor promoter and suppressor. Cancer Res. 2005 Sep 1;65(17):7782-9. [PubMed Link Image]
  5. Lokeshwar VB, Estrella V, Lopez L, Kramer M, Gomez P, Soloway MS, Lokeshwar BL: HYAL1-v1, an alternatively spliced variant of HYAL1 hyaluronidase: a negative regulator of bladder cancer. Cancer Res. 2006 Dec 1;66(23):11219-27. [PubMed Link Image]
Drug Target 7 [top]
Target 7 ID 1901
Target 7 Name CD44 antigen
Target 7 Synonyms
  1. CD44 antigen precursor
  2. CDw44
  3. ECMR-III
  4. Epican
  5. Extracellular matrix receptor-III
  6. GP90 lymphocyte homing/adhesion receptor
  7. HUTCH-I
  8. Heparan sulfate proteoglycan
  9. Hermes antigen
  10. Hyaluronate receptor
  11. PGP-1
  12. Phagocytic glycoprotein I
Target 7 Gene Name CD44
Target 7 Protein Sequence >CD44 antigen precursor
MDKFWWHAAWGLCLVPLSLAQIDLNITCRFAGVFHVEKNGRYSISRTEAADLCKAFNSTL
PTMAQMEKALSIGFETCRYGFIEGHVVIPRIHPNSICAANNTGVYILTSNTSQYDTYCFN
ASAPPEEDCTSVTDLPNAFDGPITITIVNRDGTRYVQKGEYRTNPEDIYPSNPTDDDVSS
GSSSERSSTSGGYIFYTFSTVHPIPDEDSPWITDSTDRIPATTLMSTSATATETATKRQE
TWDWFSWLFLPSESKNHLHTTTQMAGTSSNTISAGWEPNEENEDERDRHLSFSGSGIDDD
EDFISSTISTTPRAFDHTKQNQDWTQWNPSHSNPEVLLQTTTRMTDVDRNGTTAYEGNWN
PEAHPPLIHHEHHEEEETPHSTSTIQATPSSTTEETATQKEQWFGNRWHEGYRQTPREDS
HSTTGTAAASAHTSHPMQGRTTPSPEDSSWTDFFNPISHPMGRGHQAGRRMDMDSSHSTT
LQPTANPNTGLVEDLDRTGPLSMTTQQSNSQSFSTSHEGLEEDKDHPTTSTLTSSNRNDV
TGGRRDPNHSEGSTTLLEGYTSHYPHTKESRTFIPVTSAKTGSFGVTAVTVGDSNSNVNR
SLSGDQDTFHPSGGSHTTHGSESDGHSHGSQEGGANTTSGPIRTPQIPEWLIILASLLAL
ALILAVCIAVNSRRRCGQKKKLVINSGNGAVEDRKPSGLNGEASKSQEMVHLVNKESSET
PDQFMTADETRNLQNVDMKIGV
Target 7 Number of Residues 754
Target 7 Molecular Weight 81554
Target 7 Theoretical pI 5.00
Target 7 GO Classification
Function
binding
pattern binding
polysaccharide binding
glycosaminoglycan binding
hyaluronic acid binding
Process
cellular process
cell adhesion
Component
cell
membrane
Target 7 General Function Involved in hyaluronic acid binding
Target 7 Specific Function Receptor for hyaluronic acid (HA). Mediates cell-cell and cell-matrix interactions through its affinity for HA, and possibly also through its affinity for other ligands such as osteopontin, collagens, and matrix metalloproteinases (MMPs). Adhesion with HA plays an important role in cell migration, tumor growth and progression. Also involved in lymphocyte activation, recirculation and homing, and in hematopoiesis. Altered expression or dysfunction causes numerous pathogenic phenotypes. Great protein heterogeneity due to numerous alternative splicing and post-translational modification events
Target 7 Pathways Not Available
Target 7 Reactions Not Available
Target 7 Pfam Domain Function
Target 7 Signals
  • 1-20
Target 7 Transmembrane Regions
  • 650-670
Target 7 Essentiality Non-Essential
Target 7 GenBank ID Protein 180197 Link Image
Target 7 UniProtKB/Swiss-Prot ID P16070 Link Image
Target 7 UniProtKB/Swiss-Prot Entry Name CD44_HUMAN Link Image
Target 7 PDB ID 1POZ Link Image
Target 7 PDB File Show
Target 7 3D Structure
Target 7 Cellular Location
  • Membrane
  • single-pass type I membrane protein
Target 7 Gene Sequence >2229 bp
ATGGACAAGTTTTGGTGGCACGCAGCCTGGGGACTCTGCCTCGTGCCGCTGAGCCTGGCG
CAGATCGATTTGAATATAACCTGCCGCTTTGCAGGTGTATTCCACGTGGAGAAAAATGGT
CGCTACAGCATCTCTCGGACGGAGGCCGCTGACCTCTGCAAGGCTTTCAATAGCACCTTG
CCCACAATGGCCCAGATGGAGAAAGCTCTGAGCATCGGATTTGAGACCTGCAGGTATGGG
TTCATAGAAGGGCACGTGGTGATTCCCCGGATCCACCCCAACTCCATCTGTGCAGCAAAC
AACACAGGGGTGTACATCCTCACATCCAACACCTCCCAGTATGACACATATTGCTTCAAT
GCTTCAGCTCCACCTGAAGAAGATTGTACATCAGTCACAGACCTGCCCAATGCCTTTGAT
GGACCAATTACCATAACTATTGTTAACCGTGATGGCACCCGCTATGTCCAGAAAGGAGAA
TACAGAACGAATCCTGAAGACATCTACCCCAGCAACCCTACTGATGATGACGTGAGCAGC
GGCTCCTCCAGTGAAAGGAGCAGCACTTCAGGAGGTTACATCTTTTACACCTTTTCTACT
GTACACCCCATCCCAGACGAAGACAGTCCCTGGATCACCGACAGCACAGACAGAATCCCT
GCTACCACTTTGATGAGCACTAGTGCTACAGCAACTGAGACAGCAACCAAGAGGCAAGAA
ACCTGGGATTGGTTTTCATGGTTGTTTCTACCATCAGAGTCAAAGAATCATCTTCACACA
ACAACACAAATGGCTGGTACGTCTTCAAATACCATCTCAGCAGGCTGGGAGCCAAATGAA
GAAAATGAAGATGAAAGAGACAGACACCTCAGTTTTTCTGGATCAGGCATTGATGATGAT
GAAGATTTTATCTCCAGCACCATTTCAACCACACCACGGGCTTTTGACCACACAAAACAG
AACCAGGACTGGACCCAGTGGAACCCAAGCCATTCAAATCCGGAAGTGCTACTTCAGACA
ACCACAAGGATGACTGATGTAGACAGAAATGGCACCACTGCTTATGAAGGAAACTGGAAC
CCAGAAGCACACCCTCCCCTCATTCACCATGAGCATCATGAGGAAGAAGAGACCCCACAT
TCTACAAGCACAATCCAGGCAACTCCTAGTAGTACAACGGAAGAAACAGCTACCCAGAAG
GAACAGTGGTTTGGCAACAGATGGCATGAGGGATATCGCCAAACACCCAGAGAAGACTCC
CATTCGACAACAGGGACAGCTGCAGCCTCAGCTCATACCAGCCATCCAATGCAAGGAAGG
ACAACACCAAGCCCAGAGGACAGTTCCTGGACTGATTTCTTCAACCCAATCTCACACCCC
ATGGGACGAGGTCATCAAGCAGGAAGAAGGATGGATATGGACTCCAGTCATAGTACAACG
CTTCAGCCTACTGCAAATCCAAACACAGGTTTGGTGGAAGATTTGGACAGGACAGGACCT
CTTTCAATGACAACGCAGCAGAGTAATTCTCAGAGCTTCTCTACATCACATGAAGGCTTG
GAAGAAGATAAAGACCATCCAACAACTTCTACTCTGACATCAAGCAATAGGAATGATGTC
ACAGGTGGAAGAAGAGACCCAAATCATTCTGAAGGCTCAACTACTTTACTGGAAGGTTAT
ACCTCTCATTACCCACACACGAAGGAAAGCAGGACCTTCATCCCAGTGACCTCAGCTAAG
ACTGGGTCCTTTGGAGTTACTGCAGTTACTGTTGGAGATTCCAACTCTAATGTCAATCGT
TCCTTATCAGGAGACCAAGACACATTCCACCCCAGTGGGGGGTCCCATACCACTCATGGA
TCTGAATCAGATGGACACTCACATGGGAGTCAAGAAGGTGGAGCAAACACAACCTCTGGT
CCTATAAGGACACCCCAAATTCCAGAATGGCTGATCATCTTGGCATCCCTCTTGGCCTTG
GCTTTGATTCTTGCAGTTTGCATTGCAGTCAACAGTCGAAGAAGGTGTGGGCAGAAGAAA
AAGCTAGTGATCAACAGTGGCAATGGAGCTGTGGAGGACAGAAAGCCAAGTGGACTCAAC
GGAGAGGCCAGCAAGTCTCAGGAAATGGTGCATTTGGTGAACAAGGAGTCGTCAGAAACT
CCAGACCAGTTTATGACAGCTGATGAGACAAGGAACCTGCAGAATGTGGACATGAAGATT
GGGGTGTAA
Target 7 GenBank Gene ID
Target 7 GeneCard ID CD44 Link Image
Target 7 GenAtlas ID CD44 Link Image
Target 7 HGNC ID HGNC:1681 Link Image
Target 7 Chromosome Location 11
Target 7 Locus 11p13
Target 7 SNPs SNPJam Report Link Image
Target 7 General References
  1. Kugelman LC, Ganguly S, Haggerty JG, Weissman SM, Milstone LM: The core protein of epican, a heparan sulfate proteoglycan on keratinocytes, is an alternative form of CD44. J Invest Dermatol. 1992 Dec;99(6):886-91. [PubMed Link Image]
  2. Gasbarri A, Del Prete F, Girnita L, Martegani MP, Natali PG, Bartolazzi A: CD44s adhesive function spontaneous and PMA-inducible CD44 cleavage are regulated at post-translational level in cells of melanocytic lineage. Melanoma Res. 2003 Aug;13(4):325-37. [PubMed Link Image]
  3. Screaton GR, Bell MV, Jackson DG, Cornelis FB, Gerth U, Bell JI: Genomic structure of DNA encoding the lymphocyte homing receptor CD44 reveals at least 12 alternatively spliced exons. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12160-4. [PubMed Link Image]
  4. Hofmann M, Rudy W, Zoller M, Tolg C, Ponta H, Herrlich P, Gunthert U: CD44 splice variants confer metastatic behavior in rats: homologous sequences are expressed in human tumor cell lines. Cancer Res. 1991 Oct 1;51(19):5292-7. [PubMed Link Image]
  5. Harn HJ, Isola N, Cooper DL: The multispecific cell adhesion molecule CD44 is represented in reticulocyte cDNA. Biochem Biophys Res Commun. 1991 Aug 15;178(3):1127-34. [PubMed Link Image]
  6. Shtivelman E, Bishop JM: Expression of CD44 is repressed in neuroblastoma cells. Mol Cell Biol. 1991 Nov;11(11):5446-53. [PubMed Link Image]
  7. Stamenkovic I, Aruffo A, Amiot M, Seed B: The hematopoietic and epithelial forms of CD44 are distinct polypeptides with different adhesion potentials for hyaluronate-bearing cells. EMBO J. 1991 Feb;10(2):343-8. [PubMed Link Image]
  8. Brown TA, Bouchard T, St John T, Wayner E, Carter WG: Human keratinocytes express a new CD44 core protein (CD44E) as a heparan-sulfate intrinsic membrane proteoglycan with additional exons. J Cell Biol. 1991 Apr;113(1):207-21. [PubMed Link Image]
  9. Dougherty GJ, Landorp PM, Cooper DL, Humphries RK: Molecular cloning of CD44R1 and CD44R2, two novel isoforms of the human CD44 lymphocyte "homing" receptor expressed by hemopoietic cells. J Exp Med. 1991 Jul 1;174(1):1-5. [PubMed Link Image]
  10. Stamenkovic I, Amiot M, Pesando JM, Seed B: A lymphocyte molecule implicated in lymph node homing is a member of the cartilage link protein family. Cell. 1989 Mar 24;56(6):1057-62. [PubMed Link Image]
  11. 2466576 Goldstein LA, Zhou DF, Picker LJ, Minty CN, Bargatze RF, Ding JF, Butcher EC: A human lymphocyte homing receptor, the hermes antigen, is related to cartilage proteoglycan core and link proteins. Cell. 1989 Mar 24;56(6):1063-72.
  12. 7508842 Gunthert U: CD44: a multitude of isoforms with diverse functions. Curr Top Microbiol Immunol. 1993;184:47-63.
  13. 8148709 Matsumura Y, Hanbury D, Smith J, Tarin D: Non-invasive detection of malignancy by identification of unusual CD44 gene activity in exfoliated cancer cells. BMJ. 1994 Mar 5;308(6929):619-24.
  14. 8352881 Tanabe KK, Nishi T, Saya H: Novel variants of CD44 arising from alternative splicing: changes in the CD44 alternative splicing pattern of MCF-7 breast carcinoma cells treated with hyaluronidase. Mol Carcinog. 1993;7(4):212-20.
  15. 8636151 Telen MJ, Udani M, Washington MK, Levesque MC, Lloyd E, Rao N: A blood group-related polymorphism of CD44 abolishes a hyaluronan-binding consensus sequence without preventing hyaluronan binding. J Biol Chem. 1996 Mar 22;271(12):7147-53.
  16. 9580567 Peck D, Isacke CM: Hyaluronan-dependent cell migration can be blocked by a CD44 cytoplasmic domain peptide containing a phosphoserine at position 325. J Cell Sci. 1998 Jun;111 ( Pt 11):1595-601.
Target 7 Drug References
  1. Kawakami N, Nishizawa F, Sakane N, Iwao M, Tsujikawa K, Ikawa M, Okabe M, Yamamoto H: Roles of integrins and CD44 on the adhesion and migration of fetal liver cells to the fetal thymus. J Immunol. 1999 Sep 15;163(6):3211-6. [PubMed Link Image]
  2. Aguiar DJ, Knudson W, Knudson CB: Internalization of the hyaluronan receptor CD44 by chondrocytes. Exp Cell Res. 1999 Nov 1;252(2):292-302. [PubMed Link Image]
  3. Weiss L, Slavin S, Reich S, Cohen P, Shuster S, Stern R, Kaganovsky E, Okon E, Rubinstein AM, Naor D: Induction of resistance to diabetes in non-obese diabetic mice by targeting CD44 with a specific monoclonal antibody. Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):285-90. [PubMed Link Image]
  4. Laugier JP, Shuster S, Rosdy M, Csoka AB, Stern R, Maibach HI: Topical hyaluronidase decreases hyaluronic acid and CD44 in human skin and in reconstituted human epidermis: evidence that hyaluronidase can permeate the stratum corneum. Br J Dermatol. 2000 Feb;142(2):226-33. [PubMed Link Image]
  5. Okada T, Hawley RG, Kodaka M, Okuno H: Significance of VLA-4-VCAM-1 interaction and CD44 for transendothelial invasion in a bone marrow metastatic myeloma model. Clin Exp Metastasis. 1999;17(7):623-9. [PubMed Link Image]

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.